LYRM4 encodes ISD11, a critical component of the mitochondrial iron-sulfur cluster (ISC) assembly machinery that stabilizes the core ISC assembly complex and regulates the cysteine desulfurase activity of NFS1 1. The protein functions as a stabilizing factor in association with NDUFAB1 to facilitate [2Fe-2S] cluster assembly on the scaffolding protein ISCU, representing the initial step in mitochondrial iron-sulfur protein biogenesis. LYRM4 deficiency causes combined oxidative phosphorylation deficiency 19, manifesting as life-threatening cardiorespiratory episodes with hyperlactacidemia and 3-methylglutaconic aciduria 1. Beyond mitochondrial function, LYRM4 has emerged as an oncogene in multiple cancer types. Genetic variants affecting LYRM4 expression contribute to non-small cell lung cancer risk through alternative polyadenylation mechanisms 2. The gene is upregulated in hepatocellular carcinoma, where it enhances succinate dehydrogenase activity and promotes fumarate accumulation, driving tumorigenesis 3. LYRM4 expression is also elevated in glioma and correlates with poor prognosis and immune infiltration 4. Additionally, LYRM4 promoter polymorphisms are associated with cognitive deficits in schizophrenia, potentially through effects on mitochondrial oxidative phosphorylation 5.